TY - JOUR
T1 - Partitioning of Catechol Derivatives in Lipid Membranes
T2 - Implications for Substrate Specificity to Catechol- O-methyltransferase
AU - Parkkila, Petteri
AU - Viitala, Tapani
N1 - Funding Information:
This work was funded by personal thesis grants for P.P. from The Finnish Cultural Foundation and Magnus Ehrnrooth Foundation.
Publisher Copyright:
© 2020 American Chemical Society.
PY - 2020/3/18
Y1 - 2020/3/18
N2 - We have utilized multiparametric surface plasmon resonance and impendance-based quartz crystal microbalance instruments to study the distribution coefficients of catechol derivatives in cell model membranes. Our findings verify that the octanol-water partitioning coefficient is a poor descriptor of the total lipid affinity for small molecules which show limited lipophilicity in the octanol-water system. Notably, 3-methoxytyramine, the methylated derivative of the neurotransmitter dopamine, showed substantial affinity to the lipids despite its nonlipophilic nature predicted by octanol-water partitioning. The average ratio of distribution coefficients between 3-methoxytyramine and dopamine was 8.0. We also found that the interactions between the catechols and the membranes modeling the cell membrane outer leaflet are very weak, suggesting a mechanism other than the membrane-mediated mechanism of action for the neurotransmitters at the postsynaptic site. The average distribution coefficient for these membranes was one-third of the average value for pure phosphatidylcholine membranes, calculated using all compounds. In the context of our previous work, we further theorize that membrane-bound enzymes can utilize membrane headgroup partitioning to find their substrates. This could explain the differences in enzyme affinity between soluble and membrane-bound isoforms of catechol-O-methyltransferase, an essential enzyme in catechol metabolism.
AB - We have utilized multiparametric surface plasmon resonance and impendance-based quartz crystal microbalance instruments to study the distribution coefficients of catechol derivatives in cell model membranes. Our findings verify that the octanol-water partitioning coefficient is a poor descriptor of the total lipid affinity for small molecules which show limited lipophilicity in the octanol-water system. Notably, 3-methoxytyramine, the methylated derivative of the neurotransmitter dopamine, showed substantial affinity to the lipids despite its nonlipophilic nature predicted by octanol-water partitioning. The average ratio of distribution coefficients between 3-methoxytyramine and dopamine was 8.0. We also found that the interactions between the catechols and the membranes modeling the cell membrane outer leaflet are very weak, suggesting a mechanism other than the membrane-mediated mechanism of action for the neurotransmitters at the postsynaptic site. The average distribution coefficient for these membranes was one-third of the average value for pure phosphatidylcholine membranes, calculated using all compounds. In the context of our previous work, we further theorize that membrane-bound enzymes can utilize membrane headgroup partitioning to find their substrates. This could explain the differences in enzyme affinity between soluble and membrane-bound isoforms of catechol-O-methyltransferase, an essential enzyme in catechol metabolism.
KW - Catechols
KW - distribution coefficient
KW - multiparametric surface plasmon resonance
KW - partition coefficient
KW - quartz crystal microbalance
KW - supported lipid bilayer
UR - http://www.scopus.com/inward/record.url?scp=85081676889&partnerID=8YFLogxK
U2 - 10.1021/acschemneuro.0c00049
DO - 10.1021/acschemneuro.0c00049
M3 - Article
C2 - 32101397
AN - SCOPUS:85081676889
SN - 1948-7193
VL - 11
SP - 969
EP - 978
JO - ACS Chemical Neuroscience
JF - ACS Chemical Neuroscience
IS - 6
ER -